Peripheral nerve injuries affect 2-3% of trauma patients and vastly more subsequent to tumor extirpation or iatrogenic injury. These injuries can result in chronic debilitating pain from crush or neuroma formation. Patients often suffer from life-long loss or functional disturbances mediated by the injured nerve, which can severely diminish their quality of life. Nerve injuries have a tremendous socioeconomic impact from loss of work and associated healthcare costs. Nerve lesions caused by trauma, tumor or inflammatory processes often require the removal of the injured segment of nerve and subsequent repair either by tension free end-to-end neurorrhaphy or by bridging the gap with autologous nerve grafts or nerve conduits. Inadequate or untimely repair can result in lifelong deficits in muscle function or sensation.
The current standards for repairing gaps that cannot be brought together without tension require bone shortening to allow for a tension-free repair, or the use of an autologous nerve graft. These grafts are harvested from donor sensory nerves (sural nerve or posterior interosseous nerve) and have the disadvantage of loss of sensation at the donor site as well as the need for an additional surgical site. While autologous nerve grafts serve as the state-of-the-art in repairing nerve gaps, numerous challenges associated with this approach results in functional benefits to less than about 50% of patients (e.g., only about 40-50%). These challenges include morbidity at the site of harvesting of donor nerve(s), limitations to the amount of nerve that can be harvested, mismatches in size and fascicular patterns between the nerve stumps and the graft. In recent years, grafts made from biologically derived materials have gained traction over allogenic and xenogenic tissues. Collagen, fibrin, and fibronectin have been used in addition to synthetic materials such as aliphatic polyesters and hydrogels. Much progress has been made in the field of artificial nerve conduits with collagen and polyglycolic acid conduits commercially available and in use. These hollow tubes act as axon guides for the regenerating nerves and can allow for tension free bridging without the need to harvest donor nerve.
Separately, it has been shown that locally delivering growth factors or small molecules can enhance axon sprouting and peripheral nerve recovery. In animal models, a variety of proteins or small molecules including Galectin-1, VEGF, Nerve Growth Factor (“NGF”), and Netrin-1 delivered locally can act to direct axon growth, enhance Schwann cell migration and/or enhance axon regeneration. Acellular conduits and scaffolds have limited regenerative capacity and depend on the migration of supporting cells into the local environment. Local delivery of growth factors have shown promise in recruiting nerve growth promoting cells like Schwann cells and endothelial cells and in promoting direct axon growth.